Cardiovascular disease (CVD) remains the leading cause of death, and people who remain sedentary are more likely to die from CVD than from other preventable risk factors. High blood pressure is also a risk factor for CVD, and sedentary individuals are more likely to have higher blood pressure than individuals who exercise regularly. Recently, we have identified anatomical and biochemical differences in brainstem regions that control blood pressure in sedentary versus physically active animals. Specifically, neurons in the Rostral Ventrolateral Medulla (RVLM) have greater dendritic branching following sedentary conditions, the latter of which are associated with greater levels of the mature form of Brain-Derived Neurotrophic Factor (mBDNF). However, the link between increased expression of BDNF in the RVLM, increased neuroplasticity, and elevated blood pressure is unknown. The purpose of the present study was to examine the effects of BDNF overexpression in the RVLM on resting blood pressure. We hypothesized that overexpressing BDNF in the RVLM increases resting blood pressure. We used in vivo gene targeting by viral vector-mediated enhancement of BDNF expression in the RVLM of five-week-old, male Sprague-Dawley rats (n=11). Overexpression of BDNF was accomplished by injections of an AAV vector expressing either AAV/rg-CamKII-rBDNF(iso3).MYC-WPRE or AAV/rg-CamKII-EGFP-WPRE (control vector). Under isoflurane anesthesia and aseptic conditions, three 60nL microinjections of the retrograde AAV were injected bilaterally into the intermediolateral cell column of the spinal cord. Following five weeks of recovery, rats injected with the AAV vector to overexpress BDNF had significantly higher systolic blood pressure than those injected with the control viral vector (144±10 n=5 vs 117±3 mmHg n=6, p=0.019). Our results indicate the possibility that BDNF controls blood pressure by expression in the RVLM. Future studies are planned to test if hypertensive rats have overactive BDNF signaling in the RVLM (R01HL161233). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Classically, activation of gamma aminobutyric acid type A receptors (GABAA) inhibits neural excitation. Recent findings indicate that adaptations occur during pathological situations resulting in plasticity in GABAergic regulation. Depression may be such a condition. GABAA inhibition requires maintenance of low intracellular chloride ([Cl-]i) which depends upon extrusion of chloride ion by the potassium chloride co-transporter 2 (KCC2). In contrast, chloride ion is pumped into the cell by the sodium potassium two chloride co-transporter 1 (NKCC1). Downregulation of KCC2 or upregulation of NKCC1 would result in elevated [Cl-]i thereby rendering GABA less inhibitory or even excitatory. We hypothesized that inhibition of KCC2 would inhibit whereas inhibition NKCC1 would enhance GABAA inhibition within the paraventricular nucleus (PVN) of rats subjected to a chronic mild unpredictable stress (CMS) paradigm, a validated model of depression. Male and female Sprague Dawley rats were subjected to control or CMS conditions for 4 wks. MAP, heart rate and renal sympathetic nerve activity (RSNA) were assessed in conscious chronically instrumented rats at baseline and after PVN injection of 9 nmol muscimol or vehicle alone or after PVN injection of 20 pmol VU0240551 (VU; KCC2 inhibitor) or 20 pmol bumetanide (BMX, NKCC1 inhibitor). Muscimol decreased MAP and RSNA in control male and female rats but failed to do so in CMS rats. Pre-injection with VU prevented the decrease in MAP in both control and CMS rats. Unexpectedly, pre-injection with BMX also prevented the decrease in MAP in both male and female control and CMS rats. RSNA also did not decrease and actually increased in control male rats after NKCC1 inhibition (P < 0.025 vs baseline). The paradoxical response to GABAergic stimulation after NKCC1 inhibition of the PVN may be due to effects on an heterogenous population of neurons within the PVN with some neurons hyperpolarizing and others depolarizing in response to GABA stimulation. These findings are important in that they were performed in conscious animals; however, the studies are limited by the impact of inhibitors as well as muscimol on multiple neuronal populations. Future studies in individual neurons will be needed to untangle the complex relationship of neuronal elements within the PVN in both control and stress situations. Funded by VA Merit BX003480). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Consumption of foods high in salt and fructose has been increasing worldwide due to availability of fructose corn syrup and ease of consumption. As a result, the risk of cardiorenal diseases associated with high salt and fructose diet is rising. Several investigators have shown that a fructose combined with high salt diet increases blood pressure in rats. We tested the hypothesis that sodium-glucose cotransporter 5 (SGLT5) knockout will improve blood pressure. For this study, we have used male and female Sprague Dawley (SD) SGLT -/- rats in metabolic cage. After a baseline period (1 week) on 20% glucose+0.4% NaCl diet, experimental rats were randomly assigned to the following groups: 20% glucose+0.4% NaCl (Glucose-NS) and 20% fructose+4.0% NaCl (Fructose-HS) for 12 weeks. During the experimental period, food and water consumption as well as urinary excretion was assessed every 24 hours. The food consumption in Glucose-NS and Fructose-HS was 20.2 ±0.8 gm/day and 16.3±1.6 gm/day, respectively in male rats. The calories intake in Glucose-NS and Fructose-HS was 80.4±3.4 kcal/day and 58.8±5.6 kcal/day gradually. The daily water consumption was 38.2±0.8 mL and 56.5±0.7 mL in Glucose-NS and Fructose-HS respectively in male rats. The urine volume in Glucose-NS and Fructose-HS was 18.7±6.08 mL/day and 37.1±3.5 mL/day respectively in male rats. The body weight gain was comparatively lower in Fructose-HS (206±8 gm) compared to Glucose-NS (256±16 gm). However, the tibia length was same in both Glucose-NS (44.92±0.36 mm) and Fructose-HS (45.45±0.98 mm) in male rats. Moreover, the heart and the kidney weight was almost same in both group in male rats. The weight of heart was 1.91±0.25 gm and 1.50±0.16 gm in Glucose-NS and Fructose-HS respectively. Total kidney weight was 3.45±0.07 gm and 3.05± 0.19 gm in Glucose-NS and Fructose-HS groups. In contrast, the liver weight was 14.43±2.58 gm and 17.28±1.67 gm Glucose-NS and Fructose-HS groups respectively. Mean arterial pressure (MAP) was 111.73±1.27 mmHg and 110.35± 0.77 mmHg in Glucose-NS and Fructose-HS group respectively in male rats. The glomerular filtration rate (GFR) 0.27±0.01 and 0.52±0.01 ml/min/100g body weight in Glucose-NS and Fructose-HS respectively. All the results of female rats were similar to those in the male rats. In contrast to wild type rats, the SGLT5 knockout rats are resistant to increases in blood pressure when on a high salt and fructose diet. Nor did the diet alter organ weights except for liver weights. Our results demonstrated that knockout of SGLT5 transporter prevents hypertension but may still result in potential liver abnormalities. Funded by NIH R01-HL163844) This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

The present study was designed to explore whether the depletion of serotonin (5-HT) in the central nervous system (CNS5-HT) leads to systolic and diastolic dysfunction and whether this dysfunction is exacerbated by sex, age and spinal cord injury. Echocardiographic assessment of systolic and diastolic function was completed in young and old male and female tryptophan hydroxylase 2 knockout (TPH2(-/-)) and wild-type (TPH2(+/+)) mice with intact spinal cords, as well as in C-2 spinal cord hemisected young TPH2(-/-) and TPH2(+/+) mice. In addition, lumbar sympathetic nervous system activity was recorded in elderly male and female intact TPH2(-/-) and TPH2(+/+) mice. Systolic and diastolic dysfunction was evident in young TPH2(-/-) mice, including a higher left ventricular mass (P < 0.001), left ventricular outflow parameters (e.g. peak velocity) and E/A (P < 0.001). Reductions in ejection fraction and fractional shortening were also evident (P < 0.001), although stroke volume and cardiac output were maintained. The assessed dysfunction was exacerbated by age and spinal cord injury, resulting in reductions in cardiac output (P <= 0.01). The dysfunction was accompanied by increases in sympathetic burst height (P = 0.038) and incidence (P = 0.001). Reductions in CNS5-HT are coupled to systolic and diastolic dysfunction, which is exacerbated by age and spinal cord injury. This dysfunction is coupled to increases in sympathetic nervous system activity in elderly mice. Our findings are an initial step toward determining whether reductions in CNS5-HT are a unifying mechanism that links central sleep apnoea, sympathoexcitation and heart failure in intact and spinal cord injured individuals.

Hypertension is an important risk factor for cardiovascular diseases. High salt intake when consumed with excess fructose enhances hypertension and resultant cardiovascular disease. Usually, the small intestine absorbs dietary fructose, and the proximal tubule of kidney reabsorbs filtered fructose into the circulation with the help of different transporters including SGLT4 and SGLT5. Very recently, SGLT5 mRNA has also been found to be expressed in the heart. High-fructose diet stimulates the sympathetic nervous system and renin–angiotensin–aldosterone (RAAS) activity, of which both are responsible for endothelial dysfunction and are associated with salt-sensitive hypertension. Few studies exist regarding the effects of SGLT4 and SGLT5 on cardiovascular function and blood pressure. However, SGLT4 gene knockout does not alter fructose-associated impact on blood pressure. In contrast, blood pressure does not increase in SGLT5 knockout rats even during fructose consumption. Given that limiting fructose and salt consumption as a public health strategy has proven challenging, we hope that studies into SGLT4 and SGLT5 transporters will open new research initiatives to address salt-sensitive hypertension and cardiovascular disease. This review highlights current information about SGLT4 and SGLT5 on fructose absorption, salt-sensitive hypertension, cardiovascular disease and points the way for the development of therapeutic fructose inhibitors that limit adverse effects.

Marfan syndrome (MFS) is a genetic disorder caused by mutations in fibrillin-1(FBN1), which encodes FBN1, a key structural component of the extracellular matrix. Mutations in FBN1 influence the severity of aortic disease and therapeutic responses, with aortic aneurysm being the leading cause of mortality in patients with MFS. To investigate the mechanisms driving aneurysm progression, we generated a mouse model (Fbn1 Q2469X/+ ) carrying the FBN1Q2467X nonsense mutation identified in MFS patients. This mutation results in FBN1 deficiency. Although Fbn1 Q2469X/+ mice appear normal, showing only mild, nonprogressive dilation of the aortic root and ascending aorta with minor reductions in blood pressure, homozygous Fbn1 Q2469X/Q2469X mice develop spontaneous thoracic aortic aneurysms (TAA) that progress to rupture between 10 and 25 days of age, with 100% penetrance. Histopathology shows progressive vessel wall degeneration characterized by disorganized vascular smooth muscle cells, collagen loss, and elastic fiber fragmentation from early to late stages. RNA-seq analysis identifies inflammation as the dominant process in late-stage aneurysms. Immunofluorescence assay reveals inflammatory cells prominently localized to the adventitia near rupture sites, linking adventitial inflammation to aneurysm progression. This genetically modified Fbn1 Q2469X/Q2469X mouse model consistently develops progressive aortic aneurysms and provides a reliable, cost-effective platform to investigate the molecular mechanisms of aneurysm progression and to evaluate therapeutic strategies in aneurysm diseases, including Marfan syndrome and related disorders.

IntroductionThe combination of a high fructose and high salt diet typical of western diet induces high blood pressure, aortic stiffening, left ventricular (LV) diastolic dysfunction and impaired renal function in rodents. Despite an activated renin-angiotensin system (RAS) in rats fed high fructose and high salt, acute inhibition of the RAS pathway does not improve cardiac and vascular parameters. It may well be that longer term treatment is required to permit remodeling and improve cardiovascular function. Thus, we hypothesized that chronic RAS inhibition fructose+high salt-fed rats to restore blood pressure (BP) to levels similar to glucose plus normal salt-fed controls will improve cardiorenal function and histopathology.MethodsMale and female Sprague Dawley rats monitored by hemodynamic telemetry were fed 0.4% NaCl chow during baseline, then changed to chow containing either 20% glucose+0.4% NaCl (G) or 20% fructose+4% NaCl (F) and treated with vehicle, enalapril (Enal, 4 mg/kg/d) or losartan (Los, 8 mg/kg/d) by osmotic minipump for 25–26 days.ResultsBP was elevated in the fructose+high salt groups of both sexes (P < 0.05) and restored to control levels by Enal or Los. Pulse wave velocity (PWV) was lower in female F+Los rats and cardiac output higher in female F+Enal rats. GFR was not changed by diet or treatment. Fructose+high salt groups of both sexes displayed higher albuminuria that was decreased by Enal in male rats. Cardiac fibrosis and mesangial hypercellularity were greater in fructose+high salt-fed rats of both sexes and improved with either Los or Enal.DiscussionThus, inhibition of the RAS improves early changes in cardiac and renal histopathology in both sexes and albuminuria in male rats fed high fructose and high salt diet. Functional improvements in cardiorenal parameters may require longer treatment.

Combined dietary intake of fructose with high salt at levels comparable to that in the upper quintile of western population increases blood pressure, decreases glomerular filtration rate, and results in albuminuria and insulin resistance. We tested the hypothesis that chronic treatment with either an angiotensin converting enzyme inhibitor (enalapril) or angiotensin receptor blocker (losartan) will preserve glomerular filtration rate (GFR) and reduce albuminuria. Sprague Dawley rats of both sexes were instrumented with telemetry. After a baseline period on glucose+0.4% NaCl, rats were assigned to the following groups: 20% glucose+0.4%NaCl treated with vehicle (GNS+V) or 20% fructose+4% NaCl and treated with either vehicle (FHS+V), losartan 0.42 mg/kg/hr by osmotic minipump (FHS+L) or enalapril 0.21 mg/kg/hr (FHS+E). The doses of losartan and enalapril were chosen to achieve MAP similar to the control GNS+V group. Body weights did not differ among the groups upon entry into the protocol and increased similarly among the groups. Non-fasting blood glucose was elevated in all groups in both male and female rats. Mean arterial pressure (MAP) was 108±2 mmHg in GNS+V but was elevated in the FHS+V male rats, 118±2 mmHg ( P<0.01). FHS+L and FHS+E displayed MAP similar GNS+V rats: 104±2 and 106±2 mmHg, respectively. GFR assessed by transdermal FITC-sinistrin elimination was similar across all groups: 0.85±0.04 (GNS+V), 0.86±0.08 (FHS+V), 0.94±0.10 (FHS+L), 1.13±0.12 ml/min/100 g bw (FHS+E). Female rats did not display elevated MAP: 108±1 mmHg (FHS+V) vs 105±2 mmHg (GNS+V). Losartan and enalapril did not change MAP, but GFR was higher in female FHS+L rats, 1.14± 0.05, vs GNS+V 0.75±0.06 ( P < 0.05). Thus, male but not female fructose-fed rats on high salt diet display significantly higher blood pressure. Short-term fructose high salt feeding did not change GFR in either male or female rats. RAS inhibition did not impact GFR in male rats, but losartan increased GFR in female rats on high fructose plus high salt diet compared with glucose-fed female rats on normal salt diet. R01 HL163844. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Hypertension is a major cardiac risk factor. Higher blood pressures are becoming more prevalent due to changing dietary habits. Here, we evaluated the impact on blood pressure in human subjects after acutely ingesting fructose using meta-analysis. A total of 89 studies were collected from four different electronic databases from 1 January 2008 to 1 August 2023. Of these studies, 10 were selected that fulfilled all the criteria for this meta-analysis. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), and blood glucose level were analyzed using the Cohen’s d analysis or standardized mean difference at a confidence interval (CI) of 95%. The SBP, DBP, and MAP showed medium effect size; HR and glucose level displayed small effect size. The standardized mean difference of normal diet groups and fructose diet groups showed a significant increase in SBP (p = 0.04, REM = 2.30), and DBP (p = 0.03, REM = 1.48) with heterogeneity of 57% and 62%, respectively. Acute fructose ingestion contributes to an increase in arterial pressure in humans. The different parameters of arterial pressure in humans correlated with each other. These findings support further rigorous investigation, retrospective of necessity, into the effect of chronic dietary of fructose in humans in order to better understand the impact on long term arterial pressure.

Hypertension is the leading risk factor for major adverse cardiovascular events (MACE). Aortic stiffness and sympathoexcitation are robust predictors of MACE. Combined high fructose and sodium intake increases arterial pressure, aortic stiffness, renin, and sympathetic nerve activity in male rats. We hypothesized that activation of the renin angiotensin system (RAS) and/or the sympathetic system mediates aortic stiffness in rats with fructose-induced salt-sensitive blood pressure. Male and female Sprague-Dawley rats ingested 20% fructose or 20% glucose in drinking water with 0.4% NaCl chow for 1 week. Then, fructose-fed rats were switched to 4% NaCl chow (Fru + HS); glucose-fed rats remained on 0.4% NaCl chow (Glu + NS, controls for caloric intake). After 2 weeks, mean arterial pressure (MAP) and aortic pulsed wave velocity (PWV) were evaluated at baseline or after acute intravenous vehicle, clonidine, enalapril, losartan, or hydrochlorothiazide. Baseline global longitudinal strain (GLS) was also assessed. MAP and PWV were greater in male Fru + HS versus Glu + NS male rats (p < 0.05 and p < 0.001, respectively). PWV was similar between the female groups. Despite similarly reduced MAP after clonidine, PWV decreased in Fru + HS versus Glu + NS male rats (p < 0.01). Clonidine induced similar decreases in MAP and PWV in females on either diet. GLS was lower in Fru + HS versus Glu + NS male rats and either of the female groups. Thus, acute sympathoinhibition improved aortic compliance in male rats with fructose salt-sensitive blood pressure. Female rats retained aortic compliance regardless of diet. Acute RAS inhibition exerted no significant effects. Male rats on fructose high salt diet displayed an early deficit in myocardial function. Taken together, these findings suggest that adult female rats are protected from the impact of fructose and high salt diet on blood pressure, aortic stiffness, and early left ventricular dysfunction compared with male rats.

Ventricular tachyarrhythmias are common in patients with heart failure. It is one of the important preventable causes of death in these patient populations. Hypokalemia is prevalent in patients with heart failure due to various reasons. Hypokalemia can trigger ventricular arrhythmias through different mechanisms. In this case report, we present a middle-aged man with congestive heart failure (CHF) and an automated intracardiac defibrillator (AICD) on multiple diuretic medications (unintended) who presented with acute chest pain. He was found to have severe hypokalemia, hyponatremia, and an acute kidney injury. Interrogation of the AICD revealed multiple episodes of ventricular fibrillation. The patient was managed by holding his diuretic medications, cautious volume repletion, and potassium replacement. Fortunately, the patient showed rapid clinical improvement and his plasma potassium level improved. On discharge, we reconciled the patient's medications to avoid the recurrence of hypokalemia from over-diuresis and arranged a close follow-up outpatient visit with his cardiologist.

Background: Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. CVD risk increases with age; however, sex differences are known to significantly affect progression and survival. We designed this study to assess CVD-related risks associated with depression, sleep apnea, and depression comorbid with sleep apnea, in a biracial cohort of middle-aged men and women. We assessed outcomes such as left ventricular mass index (LVMI)-an index of left ventricular hypertrophy, and 3D left ventricular global longitudinal strain (3D LVGLS), an index of global myocardial function. Methods: Data were obtained from the Coronary Artery Risk Development in Young Adults (CARDIA) Study from black and white men and women (n=2778) who attended visit 9 (year 30 of follow-up) echocardiography scan. Demographics and diagnoses of depression and sleep apnea were obtained from visit 8 (year 25 of follow-up). Binary logistic regression was used to asses factors associated with high blood pressure (BP > 130/80 mmHg) and heart failure with reduced ejection fraction (HFrEF). Linear regression analyses were used to assess the strength of the following predictors: race, age, depression diagnosis and medication use for depression on LVMI and 3D LVGLS. Results: In men, depression alone and comorbid with sleep apnea were associated with higher risk of BP >130/80mmHg (OR = 1.47, p = 0.036 and OR = 2.739, p = 0.006, respectively). In both men and women (median age 55), black race was significantly associated with LVMI (p = 0.008 and p <0.001, respectively). Additional predictors of LVMI found in women were age (p = 0.019) and current medication use for depression (p = 0.006). Black race and current use of medications for depression were significantly associated with 3D LVGLS in both men (p <0.001 and p = 0.029, respectively) and women (p < 0.001 and p = 0.007, respectively). Conclusion: Our results suggest that in middle-aged women, but not men, medication-treated depression is a significant predictor of LVMI. The sex differences were not observed for 3D LVGLS. These results suggest that the severity of depression (i.e. necessitating medication use) may be an important predictor of CVD, especially in women. However, a direct effect of these medications on CVD may occur.

Psycological stress and depression are established risk factors for the development of cardiovascular disease. To model stress in rats, we use the chronic mild unpredictable stress (CMS) paradigm. We previously showed that male rats exposed to CMS for four weeks develop hypertension and that at least a part of the mechanism involves vasopressinergic signaling via V1a and V1b receptors in the paraventricular nucleus (PVN). The present investigation was designed to further ascertain the mechanistic details of hypertension and increased RSNA responses in CMS rats and to determine the hemodynamic and RSNA perturbations in female Sprague Dawley rats. We hypothesized that the increased sympathetic tone is due at least in part to the impaired GABAergic sympathoinhibition and that blockade of NKCC1 and KCC2 in the PVN will mitigate this response. Male and female Sprague Dawley rats were subjected to the CMS protocol (n = 3/group) for four weeks, while the controls were kept under standard conditions (n = 3/group). All rats were instrumented with brain cannulas directed to the PVN and allowed to recover for three days. Then, the rats were implanted with carotid arterial catheters for blood pressure measurement and a set of silver wire electrodes attached to the renal nerve for the assessment of RSNA. On study day, the rats were allowed to acclimatize to the Plexiglas study chamber for 30 minutes and the PVN was microinjected with vehicle followed by either 9 nmol of muscimol with either NKCC1 (bumetanide) or KCC2 (VU0240551) inhibitors prior to muscimol administration. MAP, heart rate (HR) and RSNA were continuously measured throughout the experiment in conscious awake rats. Male CMS rats had higher baseline MAP (133 ± 6 mmHg) and HR (435 ± 10 BPM) compared to the female CMS rats (MAP 110 ± 6 mmHg, HR 417 ± 6 BPM, P < 0.05). Microinjection of muscimol, a GABA agonist, reduced MAP and HR similarly between the male (13 ± 4 mmHg and 42 ± 16 BPM, respectively) and female (15 ± 3 mmHg and 38 ± 18 BPM, respectively) control rats. Compared to the control rats, microinjection of muscimol resulted in much smaller decrease in MAP (6 ± 5 mmHg) and HR (26 ± 17 BPM) in male rats and virtually no change in MAP (-2 ± 2 mmHg) and a similar decrease in HR (51 ± 14 BPM) in female rats. Administration of bumetanide in the PVN partially rescued the GABAergic responses to muscimol in male rats, decreasing MAP by 10 ± 2 mmHg and HR by 68 ± 31 BPM ( P < 0.001 vs. vehicle treated). Administration of VU0240551 was not effective in rescuing rescuing the muscimol responses as evidenced by a decrease in MAP by 8 ± 3 mmHg and HR by 49 ± 45 BPM (N.S. vs. vehicle treated control). These results indicate that in CMS male Sprague Dawley rats, the deranged neurocardiovascular responses are at least partially mediated by the impaired sympathoinhibitory GABA signaling, unlike in female premenopausal Sprague Dawley rats that appear to be protected from developing hypertension. This study was funded by the Department of Veteran Affairs BX003480. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Dietary fructose and salt are associated with hypertension and renal disease. Dietary input during critical postnatal periods may impact pathophysiology in maturity. The highest consumption of fructose occurs during adolescence. We hypothesized that a diet high in fructose with or without high salt in young male Sprague Dawley rats will lead to salt-sensitive hypertension, albuminuria, and decreased renal function in maturity. Four groups were studied from age 5 weeks: 20% glucose + 0.4% salt (GCS-GCS) or 20% fructose + 4% salt throughout (FHS-FHS). Two groups received 20% fructose + 0.4% salt or 20% fructose + 4% salt for 3 weeks (Phase I) followed by 20% glucose + 0.4% salt (Phase II). In Phase III (age 13-15 weeks), these two groups were challenged with 20% glucose + 4% salt, (FCS-GHS) and (FHS-GHS), respectively. Each group fed fructose in Phase I exhibited significantly higher MAP than GCS-GCS in Phase III. Net sodium balance, unadjusted, or adjusted for caloric intake and urine flow rate, and cumulative sodium balance were positive in FHS during Phase I and were significantly higher in FCS-GHS, FHS-GHS, and FHS-FHS vs GCS-GCS during Phase III. All three groups fed fructose during Phase I displayed significantly elevated albuminuria. GFR was significantly lower in FHS-FHS vs GCS-GCS at maturity. Qualitative histology showed mesangial expansion and hypercellularity in FHS-FHS rats. Thus, fructose ingestion during a critical period in rats, analogous to human preadolescence and adolescence, results in salt-sensitive hypertension and albuminuria in maturity. Prolonged dietary fructose and salt ingestion lead to a decline in renal function with evidence suggestive of mesangial hypercellularity.

Chronic stress and depression impart increased risk for adverse cardiovascular events. Autonomic dysregulation, particularly sympathoexcitation, has long been associated with poor cardiovascular outcomes. Vasopressin (AVP) receptors with the paraventricular nucleus (PVN), known as an integrating locus for hemodynamic and autonomic function, have been implicated in behavior and stress. The present studies were designed to test the hypothesis that knockdown of vasopressin V1aR within the PVN in male Sprague Dawley rats subjected to chronic mild unpredictable stress (CMS) would result in lower resting hemodynamics and renal sympathetic nerve activity (RSNA) and mitigate the responses to acute stressors. Male rats underwent CMS for 4 weeks; controls were housed in standard caging. Twenty days into the paradigm, the PVN was injected with either small interfering RNA (siRNA) directed against V1aR or scrambled RNA (scrRNA). Arterial pressure, heart rate and RSNA were ascertained by telemetry with the animals in their home cages. Pretreatment with siRNA to V1aR prevented the increase in arterial pressure to PVN microinjection with exogenous AVP. Basal mean arterial pressure (MAP) was significantly higher in scrRNA-treated but not in siRNA-treated CMS rats vs control rats. Paradoxically, basal RSNA was approximately two-fold higher in siRNA-treated CMS rats. Acute emotional stress delivered as 15-sec air-jet resulted in greater peak and duration of the MAP and RSNA responses in scrRNA-treated CMS rats vs control; siRNA treatment inhibited the responses. The 15-sec exposure to ammonia to test the nasopharyngeal reflex, whose circuitry does not include the PVN, produced similar increases in arterial pressure, heart rate, and RSNA in controls and both groups of CMS rats. Thus, CMS increases arterial pressure and predisposes to greater hemodynamic and RSNA responses to acute emotional stress. The higher basal RSNA in siRNA-treated rats may be due to functional and/or anatomical neuroplasticity occurring during more protracted inhibition of V1aR PVN signaling. Vasopressinergic signaling via V1aR in PVN modulates the cardiovascular and sympathetic responses to both the chronic and acute stress.

Fructose consumption, especially in food additives and sugar-sweetened beverages, has gained increasing attention due to its potential association with obesity and metabolic syndrome. The relationship between fructose and a high-salt diet, leading to hypertension and other deleterious cardiovascular parameters, has also become more evident, especially in preclinical studies. However, these studies have been modeled primarily on Western diets. The purpose of this review is to evaluate the dietary habits of individuals from China, Japan, and Korea, in light of the existing preclinical studies, to assess the potential relevance of existing data to East Asian societies. This review is not intended to be exhaustive, but rather to highlight the similarities and differences that should be considered in future preclinical, clinical, and epidemiologic studies regarding the impact of dietary fructose and salt on blood pressure and cardiovascular health worldwide.

Isolated hyperglycinuria is a rare disorder that is associated with osteoporosis and renal calculi. We report findings in a middle-aged, black woman who presented for renal function evaluation with a history of transient hypobicarbonataemia associated with topiramate therapy. She displayed the full triad of high urinary glycine, early-onset osteopenia despite normal reproductive hormones, and renal calculus with high urinary oxalate, phosphate and uric acid. Parathyroid hormone and fibroblast growth factor 23 were both normal. Formal genetic testing did not reveal mutations in SLC6A20, SLC6A18, SLC6A19, SLC36A2, the known genes associated with glycinuria; however, black individuals are poorly represented in the genetic databases. It may well be that otherwise unidentified mutations may be present or that topiramate may result in a lingering proximal tubule defect even after cessation of the drug.

Fructose and salt intake remain high, particularly in adolescents and young adults. The present studies were designed to evaluate the impact of high fructose and/or salt during pre- and early adolescence on salt sensitivity, blood pressure, arterial compliance, and left ventricular (LV) function in maturity. Male 5-week-old Sprague Dawley rats were studied over three 3-week phases (Phases I, II, and III). Two reference groups received either 20% glucose + 0.4% NaCl (GCS-GCS) or 20% fructose + 4% NaCl (FHS-FHS) throughout this study. The two test groups ingested fructose + 0.4% NaCl (FCS) or FHS during Phase I, then GCS in Phase II, and were then challenged with 20% glucose + 4% NaCl (GHS) in Phase III: FCS-GHS and FHS-GHS, respectively. Compared with GCS-GCS, systolic and mean pressures were significantly higher at the end of Phase III in all groups fed fructose during Phase I. Aortic pulse wave velocity (PWV) was elevated at the end of Phase I in FHS-GHS and FHS-FHS (vs. GCS-GCS). At the end of Phase III, PWV and renal resistive index were higher in FHS-GHS and FHS-FHS vs. GCS-GCS. Diastolic, but not systolic, LV function was impaired in the FHS-GHS and FHS-FHS but not FCS-FHS rats. Consumption of 20% fructose by male rats during adolescence results in salt-sensitive hypertension in maturity. When ingested with a high-salt diet during this early plastic phase, dietary fructose also predisposes to vascular stiffening and LV diastolic dysfunction in later life.

Introduction COVID-19 pandemic has been one of the main global health concerns in 2020, and many aspects of the disease remain enigmatic. While some patients infected with the disease-causing virus SARS-CoV2 have no or mild symptoms, others experience severe symptoms requiring hospitalization. Of these more severe patients, some remain stable while others experience cytokine storm syndrome or an exaggerated immune response that has been correlated with disease severity and progression of acute respiratory deterioration. It is currently unknown why some patients with COVID-19 demonstrate this response and others do not. In light of the apparent prominent role of the inflammatory mediators (i.e. cytokines) in COVID-19 pathogenesis, the ability to identify screening tools not only for the SARS-CoV2 virus but also for cytokines is important. The present investigation was designed to identify the urinary cytokine signature in COVID-19 patients. Methods The study enrolled 17 COVID-19 patients and 10 control subjects (SARS-CoV-2 negative) 18 years or older with glomerular filtration rate of > 60mL/min. Urine samples were collected and cytokines quantitated using the Luminex multiplex assay. The cytokines analyzed were growth-regulated oncogene (GRO), interleukin-8 (IL-8), and interleukin-6 (IL-6). Results The levels of GRO and IL-6 were significantly elevated in urine samples obtained from COVID-19 patients compared to controls (mean 16.8 pg/ml vs. 9.2 pg/ml ± 2.39, p < 0.0171 and mean 16.8 pg/ml vs 9.2 pg/ml ± 2.42, p < 0.0157, respectively). Conversely, IL-8 level was similar between COVID-19 patients and controls (15.6 pg/ml vs 11.3 pg/ml ± 1.3, p<0.1833). Conclusion The present investigation found that the levels of urinary cytokines GRO and IL-6 were significantly elevated in COVID-19 patients compared to controls and may serve as urinary biomarkers of disease progression. Furthermore, IL-8 although elevated in COVID-19 patients, did not reach statistical significance in our population sample. The findings of this proof of concept study underscore that the urinary cytokines may serve as prognostic and diagnostic accessible biomarkers in COVID-19.